Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice

Sandra K. Erickson, Steven R. Lear, Sean Deane, Sandrine Dubrac, Sandra L. Huling, Lien Nguyen, Jaya S. Bollineni, Sarah Shefer, Hideyuki Hyogo, David E. Cohen, Benjamin Shneider, Ephraim Sehayek, Meena Ananthanarayanan, Natarajan Balasubramaniyan, Fredrick J. Suchy, Ashok K. Batta, Gerald Salen

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Cholesterol 7α-hydroxylase, a rate-limiting enzyme for bile acid synthesis, has been implicated in genetic susceptibility to atherosclerosis. The gene, CYP7A1, encoding a protein with this activity, is expressed normally only in hepatocytes and is highly regulated. Our cyp7A1 gene knockout mouse colony, as young adults on a chow diet, is hypercholesterolemic. These mice were characterized extensively to understand how cyp7A1 affects lipid and bile acid homeostasis in different tissue compartments and whether gender plays a modifying role. Both male and female cyp7A1-deficient mice had decreased hepatic LDL receptors, unchanged hepatic cholesterol synthesis, increased intestinal cholesterol synthesis and bile acid transporters, and decreased fecal bile acids but increased fecal sterols. In females, cyp7A1 deficiency also caused changes in hepatic fatty acid metabolism, decreased hepatic canalicular bile acid transporter, Bsep, and gallbladder bile composition altered to a lithogenic profile. Taken together, the data suggest that cyp7A1 deficiency results in a proatherogenic phenotype in both genders and leads to a prolithogenic phenotype in females.

Original languageEnglish (US)
Pages (from-to)1001-1009
Number of pages9
JournalJournal of Lipid Research
Volume44
Issue number5
DOIs
StatePublished - May 2003

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Hypercholesterolemia
Bile Acids and Salts
Metabolism
Lipids
Liver
Cholesterol
Cholesterol 7-alpha-Hydroxylase
Gene encoding
LDL Receptors
Sterols
Nutrition
Phenotype
Gene Knockout Techniques
Fatty Acids
Genetic Predisposition to Disease
Genes
Gallbladder
Knockout Mice
Bile
Tissue

Keywords

  • Bile acid transporters
  • Fatty acids
  • Intestine
  • Lipid synthesis
  • Liver
  • Low density lipoprotein receptors
  • Sterol 27-hydroxylase

ASJC Scopus subject areas

  • Endocrinology

Cite this

Erickson, S. K., Lear, S. R., Deane, S., Dubrac, S., Huling, S. L., Nguyen, L., ... Salen, G. (2003). Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice. Journal of Lipid Research, 44(5), 1001-1009. https://doi.org/10.1194/jlr.M200489-JLR200

Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice. / Erickson, Sandra K.; Lear, Steven R.; Deane, Sean; Dubrac, Sandrine; Huling, Sandra L.; Nguyen, Lien; Bollineni, Jaya S.; Shefer, Sarah; Hyogo, Hideyuki; Cohen, David E.; Shneider, Benjamin; Sehayek, Ephraim; Ananthanarayanan, Meena; Balasubramaniyan, Natarajan; Suchy, Fredrick J.; Batta, Ashok K.; Salen, Gerald.

In: Journal of Lipid Research, Vol. 44, No. 5, 05.2003, p. 1001-1009.

Research output: Contribution to journalArticle

Erickson, SK, Lear, SR, Deane, S, Dubrac, S, Huling, SL, Nguyen, L, Bollineni, JS, Shefer, S, Hyogo, H, Cohen, DE, Shneider, B, Sehayek, E, Ananthanarayanan, M, Balasubramaniyan, N, Suchy, FJ, Batta, AK & Salen, G 2003, 'Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice', Journal of Lipid Research, vol. 44, no. 5, pp. 1001-1009. https://doi.org/10.1194/jlr.M200489-JLR200
Erickson, Sandra K. ; Lear, Steven R. ; Deane, Sean ; Dubrac, Sandrine ; Huling, Sandra L. ; Nguyen, Lien ; Bollineni, Jaya S. ; Shefer, Sarah ; Hyogo, Hideyuki ; Cohen, David E. ; Shneider, Benjamin ; Sehayek, Ephraim ; Ananthanarayanan, Meena ; Balasubramaniyan, Natarajan ; Suchy, Fredrick J. ; Batta, Ashok K. ; Salen, Gerald. / Hypercholesterolemia and changes in lipid and bile acid metabolism in male and female cyp7A1-deficient mice. In: Journal of Lipid Research. 2003 ; Vol. 44, No. 5. pp. 1001-1009.
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